Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis

OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanis...

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Autores principales: Magliozzi, Roberta, Hametner, Simon, Facchiano, Francesco, Marastoni, Damiano, Rossi, Stefania, Castellaro, Marco, Poli, Alberto, Lattanzi, Federico, Visconti, Andrea, Nicholas, Richard, Reynolds, Richard, Monaco, Salvatore, Lassmann, Hans, Calabrese, Massimiliano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856609/
https://www.ncbi.nlm.nih.gov/pubmed/31675181
http://dx.doi.org/10.1002/acn3.50893
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author Magliozzi, Roberta
Hametner, Simon
Facchiano, Francesco
Marastoni, Damiano
Rossi, Stefania
Castellaro, Marco
Poli, Alberto
Lattanzi, Federico
Visconti, Andrea
Nicholas, Richard
Reynolds, Richard
Monaco, Salvatore
Lassmann, Hans
Calabrese, Massimiliano
author_facet Magliozzi, Roberta
Hametner, Simon
Facchiano, Francesco
Marastoni, Damiano
Rossi, Stefania
Castellaro, Marco
Poli, Alberto
Lattanzi, Federico
Visconti, Andrea
Nicholas, Richard
Reynolds, Richard
Monaco, Salvatore
Lassmann, Hans
Calabrese, Massimiliano
author_sort Magliozzi, Roberta
collection PubMed
description OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS. METHODS: We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load. RESULTS: We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell‐related molecules, such as CXCL13, CXCL12, IL10, and BAFF. INTERPRETATION: Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B‐cell and monocyte activity are strictly correlated with cortical damage at early disease stages.
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spelling pubmed-68566092019-12-12 Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis Magliozzi, Roberta Hametner, Simon Facchiano, Francesco Marastoni, Damiano Rossi, Stefania Castellaro, Marco Poli, Alberto Lattanzi, Federico Visconti, Andrea Nicholas, Richard Reynolds, Richard Monaco, Salvatore Lassmann, Hans Calabrese, Massimiliano Ann Clin Transl Neurol Research Articles OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS. METHODS: We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load. RESULTS: We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell‐related molecules, such as CXCL13, CXCL12, IL10, and BAFF. INTERPRETATION: Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B‐cell and monocyte activity are strictly correlated with cortical damage at early disease stages. John Wiley and Sons Inc. 2019-11-01 /pmc/articles/PMC6856609/ /pubmed/31675181 http://dx.doi.org/10.1002/acn3.50893 Text en © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Magliozzi, Roberta
Hametner, Simon
Facchiano, Francesco
Marastoni, Damiano
Rossi, Stefania
Castellaro, Marco
Poli, Alberto
Lattanzi, Federico
Visconti, Andrea
Nicholas, Richard
Reynolds, Richard
Monaco, Salvatore
Lassmann, Hans
Calabrese, Massimiliano
Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
title Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
title_full Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
title_fullStr Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
title_full_unstemmed Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
title_short Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
title_sort iron homeostasis, complement, and coagulation cascade as csf signature of cortical lesions in early multiple sclerosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856609/
https://www.ncbi.nlm.nih.gov/pubmed/31675181
http://dx.doi.org/10.1002/acn3.50893
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